Spirobenzoxazinium salts, method of use and compositions thereof as antihypertensive agents

Abstract

Quaternary salts of 3,4-dihydrospiro-2H-1,3-benzoxazines are prepared by treating 3,4-dihydrospiro-2H-1,3-benzoxazines with an alkylating agent. The products are antihypertensive agents.

What is claimed is: 
     
       1. A compound of the formula: ##STR9##wherein R 1  is hydrogen, methyl or methoxy; R 2  is halo or lower alkyl;   R 3  is hydrogen, lower alkyl or lower alkoxy;   R 4  is halo, lower alkyl or trifluoromethyl;   R 5  is lower alkyl; ##STR10##is spiro-cyclohexane, spiro-cyclopentane spiro-4'-piperidine or spiro-4'-piperidine wherein the nitrogen heteroatom is substituted by lower alkanoyl and   X is halo or lower alkanoyloxy.   
     
     
       2. The compound of claim 1 with the formula: ##STR11##wherein R 2 , R 4 , R 5 , X and ##STR12##are as defined therein. 
     
     
       3. The compound of claim 1 with the formula: ##STR13##wherein R 2  is lower alkyl, R 4  is halo, and R 5 , X and ##STR14##are as defined therein. 
     
     
       4. The compound of claim 1 with the formula: ##STR15##wherein R 2  is lower alkyl, R 4  is halo, R 5  is methyl, X is halo or acetoxy and ##STR16##is defined therein. 
     
     
       5. The compound of claim 1 which is 3,3-dimethyl-3,4-dihydro-6-(1,1-dimethylethyl)-8-iodospiro[2H1,3-benzoxazinium-2,1'-cyclohexane]iodide. 
     
     
       6. The compound of claim 1 which is 3,3-dimethyl-3,4-dihydro-6-(1,1-dimethylethyl)-8-iodospiro[2H-1,3-benzoxazinium-2,1'-cyclohexane]acetate. 
     
     
       7. The compound of claim 1 which is 1'-acetyl-3,3-dimethyl-3,4-dihydro-6-(1,1-dimethylethyl)-8-iodospiro[2H-1,3-benzoxazinium-2,4'-piperidine]iodide. 
     
     
       8. The compound of claim 1 which is 3,3-dimethyl-3,4-dihydro-6-(1,1-dimethylpropyl)-8-iodospiro[2H-1,3-benzoxazinium-2,1'-cyclohexane]iodide. 
     
     
       9. A method of treating hypertension which comprises administration to a patient in need of such treatment a therapeutically effective amount of a compound of the formula: ##STR17##wherein R 1  is hydrogen, methyl or methoxy, R 2  is halo or lower alkyl;   R 3  is hydrogen, lower alkyl or lower alkoxy;   R 4  is halo, lower alkyl or trifluoromethyl;   R 5  is lower alkyl; ##STR18##is spiro-cyclohexane, spiro-cyclopentane spiro-4'piperidine or spiro-4'-piperidine wherein the nitrogen heteroatom is substituted by lower alkanoyl and   X is halo or lower alkanoyloxy.   
     
     
       10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the formula for use in treating hypertension: ##STR19##wherein R 1  is hydrogen, methyl or methoxy; R 2  is halo or lower alkyl;   R 3  is hydrogen, lower alkyl or lower alkoxy;   R 4  is halo, lower alkyl or trifluoromethyl;   R 5  is lower alkyl; ##STR20##is spiro-cyclohexane, spiro-cyclopentane spiro-4'-piperidine or spiro-4'-piperidine wherein the nitrogen heteroatom is substituted by lower alkanoyl; and   X is halo or lower alkanoyloxy.